274 BACTERIOPHAGES 



inhibits the production of a coHphage under special conditions 

 in which phage growth is supported by glycine alone. 



A detailed analysis of the effects of the tryptophan analogue, 

 5-methyltryptophan, on T2 synthesis was made by Cohen and 

 Fowler (1947). When the analogue is added at the time of 

 infection, or even during the first half of the latent period after 

 infection, phage is not formed and the adsorbed phage is eventu- 

 ally lost. When added during the latter part of the latent 

 period it behaves like other metabolic inhibitors by lysing the 

 infected cell and liberating the intracellular phage (Doermann, 

 1952). Tryptophan reverses the inhibition under conditions 

 which will also reverse the inhibition of bacterial growth. 

 Upon the addition of tryptophan to inhibited infected bacteria, 

 phage formation resumes and lysis occurs after a time which is 

 equal to the difference between the normal latent period and the 

 time interval between infection and addition of the inhibitor. 



Similar results were obtained with methionine sulfoxide, an 

 antimetabolite of glutamic acid (Fowler and Cohen, 1948). 

 Lysis and liberation of T2 is prevented by methionine sulfoxide 

 and this effect is reversed by glutamic acid. The inhibition of 

 phage growth in this instance is not complete. 



The differential action of sodium salicylate and sodium gen- 

 tisate, as inhibitors of T2 multiplication, can be reversed by 

 amino acids (Spizizen, Hampil, and Kenney, 1951). Phage 

 production in the presence of salicylate is supported by the 

 addition of tryptophan or its precursors, indole and anthranilic 

 acid. The inhibition of bacterial multiplication requires con- 

 centrations of salicylate 6 to 1 times greater than the minimal 

 concentration for phage inhibition. Bacterial inhibition, how- 

 ever, is not reversed by tryptophan but can be reversed by 

 pantothenate which has no effect of the inhibition of phage. 

 This is a unique example of differential action with respect to 

 both inhibition and its reversal. 



It is not unusual that natural amino acids may themselves 

 act as inhibitory antimetabolites of other amino acids. Serine 

 and leucine can inhibit the multiplication of T2 and the in- 



